Assembly comprising a preloaded implant and method of sterilizing the assembly

Abstract

Aspects of the present disclosure relate to a storage assembly comprising at least a portion of a delivery device and an implant. The storage assembly is configured to use its high solubility in water to capture sterilizing ethylene oxide gas and convert the escaping ethylene oxide into less harmful ethylene glycol and ethylene chlorohydrin to protect the implant from damage. In one example, the storage assembly comprises an inner container for accommodating the implant and the sterilizing solution and an outer container positioned over the inner container, wherein the outer container is at least partially filled with liquid water. The implant may be a prosthetic heart valve. Aspects of the present disclosure also relate to a method for sterilizing the storage assembly of the present disclosure.

Description

Technical Field

[0001] The present technology generally relates to a storage assembly and a method for sterilizing the storage assembly, the storage assembly including at least a portion of a transcatheter delivery device having an implant loaded thereon. In various examples, the storage assembly is at least partially sterilized with a water-soluble sterilizing gas such as ethylene oxide gas. Background Art

[0002] The human heart includes four heart valves that determine the path of blood flow through the heart: the mitral valve, tricuspid valve, aortic valve, and pulmonary valve. The mitral and tricuspid valves are atrioventricular valves, which are located between the atria and ventricles, while the aortic valve and pulmonary valve are semilunar valves, which are located between the ventricles and the arteries leaving the heart. Ideally, when a heart valve is in the open position, the valve's natural leaflets move apart from each other, and when the valve is in the closed position, the natural leaflets meet or "coapt". Problems that can occur with the valves include stenosis, in which the valve does not open properly, and / or insufficiency or regurgitation, in which the valve does not close properly. Stenosis and insufficiency can occur together in the same valve. The effects of valve dysfunction vary, with regurgitation or backflow typically having relatively serious physiological consequences for the patient.

[0003] Various different types of heart valve surgery can be used to repair or replace a diseased or otherwise defective heart valve. One conventional technique involves an open heart surgical approach performed under general anesthesia, during which the heart is stopped and blood flow is controlled by a heart-lung bypass machine.

[0004] Recently, minimally invasive methods have been developed to facilitate catheter-based implantation of valve prostheses on a beating heart, aiming to eliminate the need for the use of classic sternotomy and cardiopulmonary bypass. Generally speaking, an expandable valve prosthesis is compressed around or within a catheter of a delivery device, inserted into a patient's body lumen (such as the femoral artery), and then delivered to the desired location in the heart where the valve prosthesis is then deployed.

[0005] Known valve prostheses include a stent frame that supports the valve structure. The valve structure can take various forms and can be formed, for example, from tissue made from one or more biocompatible synthetic materials, synthetic polymers, autologous transplant tissue, homograft tissue, xenograft tissue, or one or more other suitable materials. In some embodiments, the valve structure can be formed, for example, from bovine, porcine, equine, ovine, and / or other suitable animal tissue. The valve structure can be formed from heart valve tissue, pericardium, and / or other suitable tissue. In some embodiments, the valve structure can include or form one or more leaflets. For example, the valve structure can be in the form of a trileaflet bovine pericardial valve, a bileaflet valve, or another suitable valve.

[0006] The valve prosthesis is typically packaged in a container filled with a solution, such as a glutaraldehyde solution, for sterilizing and preserving the valve prosthesis prior to attachment to a delivery device for delivery to a patient. This approach is often referred to as "wet" storage of the valve. Sometimes, the valve prosthesis is preloaded onto the distal portion of the delivery device, both of which are packaged in a container. Some known packaging configurations include both a wet compartment and a dry compartment; wherein the valve prosthesis is stored in the wet compartment that is loaded onto the delivery device assembly, and the remainder of the delivery device assembly is secured in the dry compartment.

[0007] Ethylene oxide gas is a very effective gas for sterilizing medical devices due to its high potency and ability to penetrate very deeply into the product, along the lower lumen, and through seals. That said, ethylene oxide gas is known to be very harmful to the wet valve tissue of prosthetic heart valves. The present disclosure addresses the problems and drawbacks associated with devices and methods utilizing ethylene oxide gas for sterilizing devices, including prosthetic valves. Summary of the Invention

[0008] The technology disclosed herein generally relates to a storage assembly and a method for sterilizing the storage assembly, the storage assembly comprising at least a portion of a transcatheter delivery device with an implant pre-attached thereto. Ethylene oxide gas is a very effective gas for sterilizing medical devices due to its high efficiency and ability to penetrate very deeply into the product, penetrating deep into the lumen and seals. This permeability poses a problem when attempting to sterilize artificial heart valves in a liquid sterilizing medium (such as a glutaraldehyde solution) because the reservoir seal may be damaged, allowing the ethylene oxide gas to penetrate into the valve container where it will dissolve in the sterilizing medium. Ethylene oxide gas is very harmful to moist stored artificial valve tissue. It has also been shown to form ethylene chlorohydrin and ethylene glycol when reacting with water and the commonly used BBG buffer solution used to stabilize glutaraldehyde. These cannot be removed by standard ethylene oxide vacuum processing and will remain in contact with the valve tissue for up to two years. The effects of chemical exposure during this period are unknown and are believed to pose a considerable risk to the valve tissue. Aspects of the present disclosure relate to apparatus and methods for capturing sterile ethylene oxide gas using its high solubility in water and converting the escaping ethylene oxide into less hazardous ethylene glycol and ethylene chlorohydrin.

[0009] In one aspect, the present disclosure provides a storage assembly comprising: a delivery device including a shaft having an implant loaded therein; an inner container surrounding the implant, sealing against the shaft, and containing a sterilization solution; and an outer container surrounding the inner container and sealing against the shaft. The outer container contains liquid water.

[0010] In another aspect, the present disclosure provides a method for sterilizing an assembly. The method includes providing a storage assembly, the storage assembly comprising: a delivery device having a shaft having an implant loaded therein; and an inner container surrounding the implant and being fluid-tight to the shaft. The inner container contains a sterilizing fluid. The storage assembly also includes an outer container surrounding the inner container and being fluid-tight to the shaft, and the outer container contains liquid water. The method also includes sterilizing the storage assembly with ethylene oxide gas; and converting at least a portion of the ethylene oxide gas into ethylene glycol and ethylene chlorohydrin when the at least a portion of the ethylene oxide gas contacts the liquid water.

[0011] The details of one or more aspects of the disclosure are set forth in the following drawings and description. Other features, objects, and advantages of the techniques described in this disclosure will be apparent from the description and drawings, and from the claims. BRIEF DESCRIPTION OF THE DRAWINGS

[0012] Figure 1A is a side view of a stented prosthetic heart valve in a normally expanded condition that may be used with the assemblies, devices, and methods of the present disclosure.

[0013] Figure 1B Under compression Figure 1A Side view of a prosthetic heart valve.

[0014] Figure 2A is an exploded perspective view of a delivery device according to the principles of the present disclosure.

[0015] Figure 2B yes Figure 2A Assembled top view of the delivery device.

[0016] Figure 3 is a schematic diagram of a storage assembly. DETAILED DESCRIPTION

[0017] Aspects of the present disclosure allow for the sterilization of a pre-installed transcatheter delivery device supporting an implant using ethylene oxide gas without risk of damage to the implant. As referenced herein, implants that can be used with and / or as part of the various assemblies, devices, and methods of the present disclosure can take on a variety of different configurations, such as stented transcatheter prosthetic heart valves comprising a bioprosthetic heart valve having tissue leaflets or a synthetic heart valve having polymeric, metallic, or tissue-engineered leaflets, and the implants can be specifically configured to replace any of the four valves of the human heart. Thus, stented prosthetic heart valves that can be used with the systems, devices, and methods of the present disclosure can generally be used to replace a native aortic valve, mitral valve, pulmonary valve, or tricuspid valve, or to replace a bioprosthesis that has failed in an area such as the aortic valve or mitral valve.

[0018] In general, the stented artificial heart valve of the present disclosure comprises a stent or stent frame having an inner cavity that holds a (tissue or synthetic) valve structure, wherein the stent frame has a normal expanded condition or arrangement and can be collapsed into a compressed condition or arrangement for loading within a delivery device. When released from the delivery device, the stent frame is typically configured to self-deploy or self-expand. For example, the stent or stent frame is a support structure that includes a plurality of struts or segments arranged relative to each other to provide the desired compressibility and strength to the artificial heart valve. The struts or segments are arranged so that they can self-transition from a compressed or collapsed condition to a normal radially expanded condition. The struts or segments can be formed of a shape memory material such as a nickel-titanium alloy (e.g., Nitinol). The stent frame can be laser cut from a single piece of material, or can be assembled from a plurality of discrete components.

[0019] Considering the above understanding, Figures 1A-1B A simplified, non-limiting example of an implant 10, a stented prosthetic heart valve, that can be used with the systems, devices, and methods of the present disclosure is shown in FIG. Figure 1A , showing the prosthetic heart valve 10 in a normal or expanded condition; Figure 1B The prosthetic heart valve is shown in a compressed state (e.g., when held compressed within an external catheter or sheath, as described below). The prosthetic heart valve 10 comprises a stent or stent frame 12 and a valve structure 14. A paravalvular barrier wrap (not shown) may optionally be provided around the stent frame 12. The stent frame 12 may take any of the forms mentioned above and is generally configured to be retractable from a compressed state (e.g., when held compressed within an external catheter or sheath, as described below). Figure 1B ) self-expansion, balloon expansion and / or mechanical expansion to normal expansion state ( Figure 1A ). In some embodiments, the stent framework can be self-expandable, balloon-expandable, or mechanically expandable, or a combination thereof.

[0020] The valve structure 14 can take various forms and can be formed, for example, from one or more biocompatible synthetic materials, synthetic polymers, autologous transplant tissue, allograft tissue, xenograft tissue, or one or more other suitable materials. In some embodiments, the valve structure 14 can be formed, for example, from cattle, pigs, horses, sheep, and / or other suitable animal tissues. In some embodiments, the valve structure 14 can be formed, for example, from heart valve tissue, pericardium, and / or other suitable tissues. In some embodiments, the valve structure 14 can include or form one or more leaflets 16. For example, the valve structure 14 can be in the form of a trileaflet valve, a bileaflet valve, or another suitable valve. In some configurations, the valve structure 14 can include two or three leaflets fastened together at an enlarged lateral end region to form a commissure seam, wherein the unattached edge forms the joining edge of the valve structure 14. The leaflets 16 can be fastened to a skirt, which in turn is attached to the frame 12. The upper end of the commissures can define an inflow portion 18 corresponding to a first end, or inflow end 20, of the prosthetic heart valve 10. The opposite end of the valve can define an outflow portion 22 corresponding to a second end, or outflow end 24, of the prosthetic heart valve 10. As shown, the stent frame 12 can have a lattice or cell-like structure and optionally form or provide crowns 26 and / or eyelets 28 (or other shapes) at the outflow end 24 and the inflow end 20.

[0021] pass Figure 1A and 1B In one exemplary configuration, the prosthetic heart valve 10 can be configured (e.g., sized and shaped) to replace or repair an aortic valve. Alternatively, other shapes adapted to mimic the specific anatomy of the valve to be repaired are also contemplated (e.g., the shape and / or size of a stented prosthetic heart valve that can be used with the present disclosure can alternatively be designed to replace a native mitral valve, pulmonary valve, or tricuspid valve or for compassionate use, such as an ectopic implant).

[0022] Considering the above understanding of some example implant valves, Figure 2A and 2B One embodiment of a delivery device 50 for percutaneously delivering a self-expanding implant is shown in simplified form in FIG. The delivery device 50 includes an optional delivery sheath assembly 52, a shaft assembly 54 having a valve retaining member or main shaft 56, and a handle assembly 58. Details of the various components are provided below. However, in general, the delivery device 50 is used with an implant (e.g., Figures 1A-1BThe delivery device 50 is combined with the prosthetic heart valve of the present invention to form a system for performing a treatment procedure. The delivery device 50 provides a loaded state or delivery state, wherein the implant is loaded onto the main shaft 56 and is compressed and held within the capsule 62 of the delivery sheath assembly 52. The delivery sheath assembly 52 can be manipulated to remove the capsule 62 proximally from the prosthetic heart valve by operating the handle assembly 58, thereby allowing the prosthetic heart valve to self-expand and partially release from the main shaft 56. When the capsule 62 is retracted proximally, the implant can be fully released or deployed from the delivery device 50. As desired, the delivery device 50 can optionally include other components that assist, promote, or control the full deployment of the implant.

[0023] Can be modified Figure 2A and 2B Various features of components 52-58 as reflected in and described below may be modified or replaced with different structures and / or mechanisms. Thus, the present disclosure is in no way limited to the delivery sheath assembly 52, shaft assembly 54, or handle assembly 58 shown and described below. Further, delivery device 50 may optionally include additional components or features, such as a flush port assembly 72, a recapture sheath (not shown), etc.

[0024] In some embodiments, the optional delivery sheath assembly 52 defines a proximal end 80 and a distal end 82 and includes a balloon 62 and an outer shaft 84. The delivery sheath assembly 52 can be similar to a catheter, defining an inner lumen 86 (generally referred to as "lumen 86") extending from the distal end 82 through the balloon 62 and at least a portion of the outer shaft 84. The inner lumen 86 can be open at the proximal end 80 (e.g., the outer shaft 84 can be a tube). The balloon 62 extends distally from the outer shaft 84 and, in some embodiments, has a stiffer construction (compared to the stiffness of the outer shaft 84) that exhibits radial or circumferential stiffness sufficient to significantly resist the expected expansion forces of the implant (not shown) when compressed within the balloon 62. For example, the outer shaft 84 can be a polymer tube embedded with a metal braid, while the balloon 62 comprises a laser-cut metal tube optionally embedded within a polymer covering. Alternatively, the balloon 62 and outer shaft 84 can have a more uniform or even uniform construction (e.g., a continuous polymer tube). Regardless, the balloon 62 is configured to compressively hold the stented prosthetic heart valve at a predetermined diameter when loaded within the balloon 62, and the outer shaft 84 is used to connect the balloon 62 to the handle assembly 58. The outer shaft 84 (and the balloon 62) is configured to be sufficiently flexible for traversing the patient's vasculature, yet still exhibit sufficient longitudinal stiffness to achieve the desired axial movement of the balloon 62. In other words, proximal retraction of the outer shaft 84 is directly transmitted to the balloon 62 and results in a corresponding proximal retraction of the balloon 62. In other embodiments, the outer shaft 84 is further configured to transmit a rotational force or movement to the balloon 62.

[0025] The shaft assembly 54 can have various configurations suitable for supporting the delivery sheath assembly 52 and the implant relative to the capsule 62. In some embodiments, the inner shaft assembly 54 includes an intermediate shaft or tube 90 and a proximal shaft or tube 92. The intermediate tube 90 is optionally formed of a flexible polymer material (e.g., PEEK) and is sized to be slidably received within the delivery sheath assembly 52. The intermediate tube 90 serves as a transition to the deflection assembly 60, and in some embodiments, the intermediate tube is a flexible polymer tube (e.g., PEEK) having a diameter slightly smaller than that of the proximal tube 92. The proximal tube 92 can have a more rigid configuration that is configured for robust assembly with a handle assembly 58, such as a metal hypotube. Other configurations are also contemplated. For example, in other embodiments, the intermediate tube 90 and the proximal tube 92 are integrally formed into a single, uniform tube or shaft. In any case, the inner shaft assembly 54 forms or defines at least one lumen (not shown) sized to, for example, slidably receive a guidewire (not shown).

[0026] The main shaft 56 of the inner shaft assembly 54 includes an inner support shaft 74 and a tip 76. The inner support shaft 74 is sized to be slidably received within the inner cavity 86 of the delivery sheath assembly 52 and is configured for mounting to the deflection assembly 60. The inner support shaft 74 can be a flexible polymer tube embedded with a metal braid. Other configurations are also acceptable as long as the inner support shaft 74 exhibits sufficient structural integrity to support a loaded, compressed stented artificial heart valve (not shown). The tip 76 forms or defines a nose cone having an outer surface that tapers distally and is suitable for promoting atraumatic contact with body tissue. The tip 76 can be fixed or slidable relative to the inner support shaft 74. The main shaft 56 can define a continuous inner cavity (not shown) that is sized to slidably receive auxiliary components such as a guide wire (not shown).

[0027] The handle assembly 58 generally includes a housing 66 and one or more actuator mechanisms 68 (generally referred to herein). The housing 66 holds the one or more actuator mechanisms 68, wherein the handle assembly 58 is configured to facilitate sliding movement of the delivery sheath assembly 52 relative to other components (e.g., the inner shaft assembly 54, the main shaft 56). The housing 66 can have any shape or size suitable for convenient handling by the user.

[0028] In view of the above general description of exemplary embodiments of the components of the delivery device 50, the present disclosure provides a number of assemblies for storing an implant in a "wet" (typically immersed in a sterilization fluid) state with at least a portion of a delivery device (e.g., an inner shaft assembly or main shaft of a delivery device such as the delivery device 50). The disclosed embodiments are configured to allow sterilization of the implant as well as the portion of the delivery device included in the storage assembly. In the embodiments disclosed herein, the implant can be stored in an expanded state or a compressed state.

[0029] When the implant is pre-loaded into a delivery device for storage prior to use, it is generally desirable to store the implant "wet" (ie, in a sterilizing fluid such as glutaraldehyde BBG solution). Figure 3 , an embodiment of a storage assembly 1 for wet storage of implants is shown in FIG. The storage assembly 1 includes an implant 10 preloaded onto a shaft assembly 54 of a delivery device 50. It should be understood that the implant 10 and delivery device 50 are provided as examples only, and the present disclosure is not intended to be limited to any particular implant or delivery device. Further, in this embodiment, the implant 10 is loaded onto and packaged with only a selected portion of the complete delivery device 50, as the delivery device 50 is not required to be a part of the storage assembly 1 in its entirety. In one example, the handle assembly 58 or other potentially reusable components of the delivery device 50 can be omitted and placed together prior to use.

[0030] exist Figure 3 In one example, the storage assembly 1 includes a delivery device 50 including a shaft 54 having an artificial heart valve 10 loaded thereto. It should be understood that the shaft 54 can be a continuous member or can optionally include a separate main shaft 56. The storage assembly 1 also includes an inner container 90 that surrounds the artificial heart valve 10 and seals the shaft 54. In one example, the inner container 90 is made of a flexible polymer. The inner container 90 is sealed to the shaft 54 with a fluid-tight seal 92 (such as a silicone seal) so that a sterilizing fluid 94 (referenced as a whole) located within an internal compartment 96 of the inner container 90 is retained therein. In one example, the sterilizing fluid 94 includes glutaraldehyde and a buffer (e.g., BBG) in solution.

[0031] The storage assembly 1 also includes an outer container 100 that surrounds the inner container 90 and seals the shaft with a fluid-tight seal 104 (such as a silicone seal). In one example, the seal 104 can be part of the cap 102. The outer container 100 contains liquid water 106 (referenced as a whole). For example, the liquid water 106 can contain up to 100% purified water or distilled water. The outer container 100 is filled with a sufficient amount of liquid water 106 so that during a sterilization process including ethylene oxide gas EO (schematically represented), any ethylene oxide gas EO that escapes through the seal 104 between the shaft 54 and the outer container 100 must pass through the water 106 before it can potentially pass through the seal 92 between the shaft 54 and the inner container 90 (where the ethylene oxide gas EO could damage the artificial heart valve 10). In one embodiment, there is a sufficient amount of liquid water to cover the inner container and the first seal, regardless of how the storage assembly is oriented. Chemical byproducts of the reaction of ethylene oxide gas EO with water (e.g., water 106) include ethylene glycol and ethylene chlorohydrin. In various embodiments, outer container 100 may additionally include activated carbon 110, which can absorb ethylene glycol and ethylene chlorohydrin that may be generated during ethylene oxide gas sterilization. For example, activated carbon 110 can be provided in the form of strips or pellets positioned within interior 108 of outer container 100. It is believed, but not relied upon, that the reaction of ethylene oxide gas EO to ethylene glycol and ethylene chlorohydrin can be accelerated by acidifying water 106. For example, water 106 can be acidified with citric acid or the like.

[0032] Various methods of the present disclosure may first include providing a storage assembly 1 of the present disclosure, which includes at least a portion of a delivery device. In one example, the provided portion of the delivery device 50 includes a shaft 54 (optionally including a main shaft 56) having an implant or artificial valve 10 loaded thereon. The storage assembly 1 has an inner container 90 that surrounds the implant 10 and seals the shaft 54 / 56, and the inner container 90 contains a sterilizing liquid 96. The storage assembly 1 also includes an outer container 100 that surrounds the inner container 90 and seals the shaft 54 / 56. The outer container 100 contains liquid water 106. The method also includes sterilizing the storage assembly 1 with ethylene oxide gas EO in any known manner 204. If any ethylene oxide EO gas destroys the seal 104, the ethylene oxide gas EO will contact the liquid water 106 and react to form ethylene glycol and ethylene chlorohydrin. In some methods of the present disclosure, outer container 100 further contains activated carbon 110 disposed within interior 108 , and the method further includes activated carbon 110 absorbing at least a portion of any ethylene glycol and ethylene chlorohydrin 206 present within interior 108 .

[0033] It should be understood that the various aspects disclosed herein can be combined in combinations different from those specifically given in the description and drawings. It should also be understood that, depending on the example, certain actions or events of any process or method described herein can be performed in a different order, can be added, combined, or omitted entirely (e.g., not all described actions or events may be required to perform the technique). In addition, although for clarity, certain aspects of the present disclosure are described as being performed by a single module or unit, it should be understood that the techniques of the present disclosure can be performed by a combination of units or modules associated with, for example, a medical device.

Claims

1. A storage assembly, comprising: a delivery device comprising a shaft having an implant loaded thereto; an inner container surrounding the implant and sealing the shaft; wherein the inner container contains a sterilization fluid; and an outer container surrounding the inner container and sealing against the shaft; The outer container contains liquid water.

2. The storage assembly of claim 1, wherein the outer container contains activated carbon.

3. The storage assembly of claim 1 or 2, wherein the implant is an artificial heart valve.

4. The storage assembly of claim 1 or 2, wherein the inner container is sealed to the shaft with a first seal; wherein there is a sufficient amount of liquid water to cover the inner container and the first seal.

5. The storage assembly of claim 4, wherein a sufficient amount of liquid water is present to cover the inner container and the first seal regardless of the orientation of the storage assembly.

6. The storage assembly of claim 1 or 2, wherein the liquid water is selected from the group consisting of purified water and distilled water.

7. The storage assembly of claim 1 or 2, wherein the sterilizing fluid comprises glutaraldehyde. The storage assembly of claim 7 , wherein the sterilizing fluid comprises a buffer solution.

9. A method of sterilizing an assembly, the method comprising: A storage assembly is provided, the storage assembly comprising: A delivery device comprising: a shaft having an implant loaded thereto; an inner container surrounding the implant and being fluid-tight to the shaft; wherein the inner container contains a sterilization fluid; and an outer container surrounding the inner container and being fluid-tight to the shaft; wherein the outer container contains liquid water; sterilizing the storage assembly with ethylene oxide gas; and When at least a portion of the ethylene oxide gas contacts the liquid water, the portion of the ethylene oxide gas is converted into ethylene glycol and ethylene chlorohydrin.

10. The method of claim 9, wherein the outer container further contains activated carbon, and the method further comprises allowing the activated carbon to absorb at least a portion of the ethylene glycol and the ethylene chlorohydrin.

11. A method according to claim 9 or 10, wherein the inner container is sealed to the shaft with a first seal; wherein a sufficient amount of liquid water is present to cover the inner container and the first seal.

12. The method of claim 11, wherein a sufficient amount of liquid water is present to cover the inner container and the first seal regardless of the orientation of the storage assembly.

13. The method according to claim 9 or 10, wherein the liquid water is selected from the group consisting of deionized water and distilled water.

14. The method according to claim 9 or 10, wherein the sterilizing solution comprises glutaraldehyde. The method according to claim 14 , wherein the sterilizing solution comprises a buffer solution.

16. The method of claim 9 or 10, wherein the implant is a prosthetic heart valve.

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